The development and validation of the pandemic medication-assisted treatment questionnaire for the assessment of pandemic crises impact on medication management and administration for patients with opioid use disorders

0000-0002-5221-921

Race and Inflammatory Bowel Disease in an Urban Healthcare System

Inflammatory bowel disease (IBD) is increasingly common among non-Caucasian populations, but interracial differences in disease characteristics and management are not well-characterized. We tested the hypothesis that disease characteristics and management vary by race among IBD patients in an ethnically diverse healthcare system. A retrospective study of the safety net healthcare system of San Francisco, CA, from 1996 to 2009 was undertaken. Patient records with International Classification of Diseases, 9th Revision (ICD9) codes 555.xx, 556.xx, and 558.xx were reviewed. Adult patients with confirmed IBD diagnoses were included. Interracial variations in disease characteristics and management were assessed broadly; focused between-race comparisons identified specific differences. The 228 subjects included 77 (33.4%) with Crohn’s disease (CD), 150 (65.8%) with ulcerative colitis, and 1 (0.4%) with IBD, type unclassified. The race distribution included 105 (46.1%) white, 34 (14.9%) black, 35 (15.4%) Hispanic, and 51 (22.4%) Asian subjects. Asians and Hispanics were diagnosed at older ages (41.0 and 37.1 years, respectively) and had shorter disease durations (5.4 and 5.2 years, respectively) than whites (30.5 years at diagnosis and 8.6 years duration, P < 0.05) and blacks (31.7 years at diagnosis and 12.1 years duration, P < 0.05). CD was more common among blacks (50% of subjects) than Asians (25.5% of subjects, P = 0.015). The Montreal classification of IBD was similar among races. Hispanics were less likely than others to be treated with 5-aminosalicylates (5-ASA), immunomodulators, and steroids. Medical and surgical management was otherwise similar among races. Modest race-based differences in IBD characteristics exist in this racially diverse healthcare system, but the management of IBD is similar among race groups

Extended optical treatment versus early patching with an intensive patching regimen in children with amblyopia in Europe (EuPatch): a multicentre, randomised controlled trial

Background: Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial. Methods: EuPatch was a randomised controlled trial conducted in 30 hospitals in the UK, Greece, Austria, Germany, and Switzerland. Children aged 3–8 years with newly detected, untreated amblyopia (defined as an interocular difference ≥0·30 logarithm of the minimum angle of resolution [logMAR] best corrected visual acuity [BCVA]) due to anisometropia, strabismus, or both were eligible. Participants were randomly assigned (1:1) via a computer-generated sequence to either the EOT group (18 weeks of glasses use before patching) or to the early patching group (3 weeks of glasses use before patching), stratified for type and severity of amblyopia. All participants were initially prescribed an intensive patching regimen (10 h/day, 6 days per week), supplemented with motivational materials. The patching period was up to 24 weeks. Participants, parents or guardians, assessors, and the trial statistician were not masked to treatment allocation. The primary outcome was successful treatment (ie, ≤0·20 logMAR interocular difference in BCVA) after 12 weeks of patching. Two primary analyses were conducted: the main analysis included all participants, including those who dropped out, but excluded those who did not provide outcome data at week 12 and remained on the study; the other analysis imputed this missing data. All eligible and randomly assigned participants were assessed for adverse events. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN51712593) and is no longer recruiting. Findings: Between June 20, 2013, and March 12, 2020, after exclusion of eight participants found ineligible after detailed screening, we randomly assigned 334 participants (170 to the EOT group and 164 to the early patching group), including 188 (56%) boys, 146 (44%) girls, and two (1%) participants whose sex was not recorded. 317 participants (158 in the EOT group and 159 in the early patching group) were analysed for the primary outcome without imputation of missing data (median follow-up time 42 weeks [IQR 42] in the EOT group vs 27 weeks [27] in the early patching group). 24 (14%) of 170 participants in the EOT group and ten (6%) of 164 in the early patching group were excluded or dropped out of the study, mostly due to loss to follow-up and withdrawal of consent; ten (6%) in the EOT group and three (2%) in the early patching group missed the 12 week visit but remained on the study. A higher proportion of participants in the early patching group had successful treatment (107 [67%] of 159) than those in the EOT group (86 [54%] of 158; 13% difference; p=0·019) after 12 weeks of patching. No serious adverse events related to the interventions occurred. Interpretation: The results from this trial indicate that early patching is more effective than EOT for the treatment of most children with amblyopia. Our findings also provide data for the personalisation of amblyopia treatments. Funding: Action Medical Research, NIHR Clinical Research Network, and Ulverscroft Foundation

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Extended optical treatment versus early patching with an intensive patching regimen in children with amblyopia in Europe (EuPatch): a multicentre, randomised controlled trial

Background Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial. Methods EuPatch was a randomised controlled trial conducted in 30 hospitals in the UK, Greece, Austria, Germany, and Switzerland. Children aged 3–8 years with newly detected, untreated amblyopia (defined as an interocular difference ≥0·30 logarithm of the minimum angle of resolution [logMAR] best corrected visual acuity [BCVA]) due to anisometropia, strabismus, or both were eligible. Participants were randomly assigned (1:1) via a computer-generated sequence to either the EOT group (18 weeks of glasses use before patching) or to the early patching group (3 weeks of glasses use before patching), stratified for type and severity of amblyopia. All participants were initially prescribed an intensive patching regimen (10 h/day, 6 days per week), supplemented with motivational materials. The patching period was up to 24 weeks. Participants, parents or guardians, assessors, and the trial statistician were not masked to treatment allocation. The primary outcome was successful treatment (ie, ≤0·20 logMAR interocular difference in BCVA) after 12 weeks of patching. Two primary analyses were conducted: the main analysis included all participants, including those who dropped out, but excluded those who did not provide outcome data at week 12 and remained on the study; the other analysis imputed this missing data. All eligible and randomly assigned participants were assessed for adverse events. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN51712593) and is no longer recruiting. Findings Between June 20, 2013, and March 12, 2020, after exclusion of eight participants found ineligible after detailed screening, we randomly assigned 334 participants (170 to the EOT group and 164 to the early patching group), including 188 (56%) boys, 146 (44%) girls, and two (1%) participants whose sex was not recorded. 317 participants (158 in the EOT group and 159 in the early patching group) were analysed for the primary outcome without imputation of missing data (median follow-up time 42 weeks [IQR 42] in the EOT group vs 27 weeks [27] in the early patching group). 24 (14%) of 170 participants in the EOT group and ten (6%) of 164 in the early patching group were excluded or dropped out of the study, mostly due to loss to follow-up and withdrawal of consent; ten (6%) in the EOT group and three (2%) in the early patching group missed the 12 week visit but remained on the study. A higher proportion of participants in the early patching group had successful treatment (107 [67%] of 159) than those in the EOT group (86 [54%] of 158; 13% difference; p=0·019) after 12 weeks of patching. No serious adverse events related to the interventions occurred. Interpretation The results from this trial indicate that early patching is more effective than EOT for the treatment of most children with amblyopia. Our findings also provide data for the personalisation of amblyopia treatments. Funding Action Medical Research, NIHR Clinical Research Network, and Ulverscroft Foundation

WSES guidelines for management of Clostridium difficile infection in surgical patients

In the last two decades there have been dramatic changes in the epidemiology of Clostridium difficile infection (CDI), with increases in incidence and severity of disease in many countries worldwide. The incidence of CDI has also increased in surgical patients. Optimization of management of C difficile, has therefore become increasingly urgent. An international multidisciplinary panel of experts prepared evidenced-based World Society of Emergency Surgery (WSES) guidelines for management of CDI in surgical patients.Peer reviewe

Modelling the effect of temperature and CO 2 on microbial spoilage of chilled gilthead seabream fillets

The effect of temperature (0-15°C) and CO 2 (0-80%) on the growth of spoilage bacteria (total viable count, Pseudomonas sp. and lactic acid bacteria) in marine cultured gilthead seabream fillets was studied and kinetically modelled using an Arrhenius type equation. Pseudomonas sp. dominated the spoilage microflora of aerobically packed fillets whereas LAB defined spoilage at the MAP conditions. Modified atmosphere packaging led to a significant shelf-life extension of fillets, in terms of microbial growth and organoleptic deterioration. The preservative effect of CO 2 was greater as the CO 2 concentration in the atmosphere increased. Under this context, MAP can practically extend the shelf life of chilled gilthead seabream fillets. The growth of LAB was modelled as a function of temperature and CO 2 concentration in modified atmosphere packaging. The applicability of the models was validated at fluctuating temperature conditions. The nominal maximum CO 2 concentration (CO 2,max) for growth and the specific growth rate (k ref) at T ref (4°C) in the absence of carbon dioxide were determined to be 98.3% and 0.015 h -1, respectively. The activation energy parameter of the model, which indicates the temperature dependence of the growth rates, was 101.0 kJ/mol showing a strong dependence of LAB growth on storage temperature. Based on organoleptic acceptability the end of shelf life coincided with 10 7/g Pseudomonas sp. and 10 6/g lactobacilli for aerobically and MAP stored samples respectively. Based on the developed models this translates to 7, 8, 12 and 32 days of shelf life at 5°C and 0, 20, 50 and 80% CO 2 respectively